Antimalarial activity of nepodin isolated from Rumex crispus

Abstract

The purpose of this study is to define the antimalarial activity of Rumex crispus. To identify an active compound that is isolated from R. crispus, bioassay-based chromatographic fractionation and purification is carried out from 70 % ethanol extract of R. crispus; then, an active compound, nepodin, is identified by spectroscopic analysis. Anitmalarial activity is measured by PfNDH2 assay, cytotoxicity, and animal test. From NADH:quinone oxidoreductase enzyme (PfNDAH2) assay, nepodin exhibited significant IC50 values that were 0.74 ± 0.07 and 0.79 ± 0.06 μg/ml against P. falciparum chloroquine-sensitive (3D7) and P. falciparum chloroquine-resistant (S20), respectively. Nepodin showed a potential selective inhibition (SI index: ratio of 50 % cytotoxic concentration to 50 % effective anti-plasmodial concentration) of 161.6 and 151.4 against P. falciparum 3D7 and P. falciparum S20. In the animal test, all groups of nepodin treatment of 10, 50, and 250 mg/kg were active with a parasitemia suppression of 97.1 ± 3.3, 99.1 ± 3.7, and 99.1 ± 2.6 %, respectively. The survival time with nepodin treatment was increased by 14.6 ± 2.5, 16.2 ± 1.5, and 19.8 ± 1.7 days at each dose, respectively. This study newly identified the plant R. crispus containing nepodin, which is a potential antimalarial compound. It exhibited the inhibitory activity of PfNDH2 and prolonged the survival time on the group of nepodin treatment; moreover, it inhibited the parasitemia in the animal test.

This is a preview of subscription content, access via your institution.

References

  1. Breman, J.G. 2001. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. American Journal of Tropical Medicine and Hygiene 64: 1–11.

    PubMed  CAS  Google Scholar 

  2. Carmichael, J., W.G. Degraff, A.F. Gazdar, J.D. Minna, and J.B. Mitchell. 1987. Evaluation of a tetrazolium based semiautomated colorimetric assay. I: assessment of chemosensitivity testing. Cancer Research 47: 936–942.

    PubMed  CAS  Google Scholar 

  3. Colegate, S.M., P.R. Dorling, and C.R. Huxtable. 1985. Stypandrol, a toxic binaphthalentetrol isolated from Stypandra imbricata. Australian Journal of Chemistry 38: 1233–1241.

    Article  CAS  Google Scholar 

  4. Fang, J., and D.S. Beattie. 2003. External alternative NADH dehydrogenase of Saccharomyces cerevisiae: a potential source of superoxide. Free Radical Biology & Medicine 34: 478–488.

    Article  CAS  Google Scholar 

  5. Garham, P.C.C. 1966. Malaria parasites and other haemosporidia, 470. Oxford: Blackwell.

    Google Scholar 

  6. Ghosh, L., J.R. Gayen, S. Sinha, S. Pal, M. Pal, and B.P. Saha. 2003. Antibacterial efficacy of Rumex nepalensis Spreng. roots. Phytotherapy Research: PTR 17: 558–559.

    PubMed  Article  Google Scholar 

  7. Gupta, L.M., and R. Raina. 1998. Side effects of some medicinal plants. Current Science 75: 897–900.

    Google Scholar 

  8. Jančić, R., V. Janjatović, M. Obradović, S. Pavlović, P. Lukić, and N. Krstić-Pavlović. 1989. Rumex. In Medicinal Plants of SR Serbia, ed. M. Sarić, 494–497. Belgrade: Serbian Academy of Sciences and Arts.

    Google Scholar 

  9. Lenaz, G., R. Fato, A. Baracca, and M.L. Genova. 2004. Mitochondrial quinone reductases: complex I. Methods in Enzymology 382: 3–20.

    PubMed  Article  CAS  Google Scholar 

  10. Li, X.H., and J.L. McLaughlin. 1989. Bioactive compounds from the root of Myrsine africana. Journal of Natural Products 52: 660–662.

    PubMed  Article  CAS  Google Scholar 

  11. Liu, J., Z.T. Xia, G.R. Zhou, L.L. Zhang, and L.Y. Kong. 2011. Study on the chemical constituents of Rumex patientia. Zhong Yao Cai 34: 893–895.

    PubMed  CAS  Google Scholar 

  12. Meshnick, S.R. 2001. Artemisinin and its derivatives. In Anti-malarial chemotherapy: mechanisms of action, resistance, and new directions in drug discovery, ed. P.J. Rosenthal, 191–201. Totowa: Humana.

    Google Scholar 

  13. Muganga, R., L. Angenot, M. Tits, and M. Frédérich. 2010. Antiplasmodial and cytotoxic activities of Rwandan medicinal plants used in the treatment of malaria. Journal of Ethnopharmacology 128: 52–57.

    PubMed  Article  Google Scholar 

  14. Olliaro, P.L., and P.B. Bloland. 2001. Clinical and public health implications of anti-malarial drug. In Drug discovery, ed. P.J. Rosenthal, 65–83. Totowa: Humana.

    Google Scholar 

  15. Omulokoli, E., B. Khan, and S.C. Chhabra. 1997. Antiplasmodial activity of four Kenyan medicinal plants. Journal of Ethnopharmacology 56: 133–137.

    PubMed  Article  CAS  Google Scholar 

  16. Pal, S.K., and Y. Shukla. 2003. Herbal medicine: current status and the future. Asian Pacific Journal of Cancer Prevention: APJCP 4: 281–288.

    PubMed  Google Scholar 

  17. Pekrun, C., D. Jund, V. Hofrichter, S. Wagner, U. Thuman, and W. Claupein. 2002. Pflanzen- und ackerbauliche Maßnahmen zur Ampferbekämpfung auf Acker- und Grünlandflächen unter den Produktionsbedingungen des Ökologischen Landbaus. Journal of Plant Diseases and Protection 18: 533–540.

    Google Scholar 

  18. Peters, W., and B.L. Robinson. 1992. The chemotherapy of rodent malarial: studies on pyronaridine and other manich base antimalarials. Annals of Tropical Medicine and Parasitology 86: 455–465.

    PubMed  CAS  Google Scholar 

  19. Plowe, C.V., A. Djimde, M. Bouare, O. Doumbo, and T.E. Wellens. 1995. Pyrimethamine and proguanil resistance-conferring mutation in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. American Journal of Tropical Medicine and Hygiene 52: 565–568.

    PubMed  CAS  Google Scholar 

  20. Rasoanaivo, P., A. Petitjean, S. Ratsimamanga-Urverg, and A. Rakoto-Ratsimamanga. 1992. Medicinal plants used to treat malaria in Madagascar. Journal of Ethnopharmacology 37: 117–127.

    PubMed  Article  CAS  Google Scholar 

  21. Snow, R.W., J.F. Trape, and K. Marsh. 2001. The past, present and future of childhood malaria mortality in Africa. Trends in Parasitology 17: 593–597.

    PubMed  Article  CAS  Google Scholar 

  22. Suh, H.J., K.S. Lee, S.R. Kim, M.H. Shin, S. Park, and S. Park. 2011. Determination of singlet oxygen quenching and protection of biological systems by various extracts from seed of Rumex crispus L. Journal of Photochemistry and Photobiology B: Biology 102: 102–107.

    Article  CAS  Google Scholar 

  23. Tona, L., and K. Mesia. 2001. In-vivo antimalarial activity of Cassia occidentalis, Morinda morindoides and Phyllanthus niruri. Annals of Tropical Medicine and Parasitology 95: 47–57.

    PubMed  Article  CAS  Google Scholar 

  24. Trager, W., and J.B. Jensen. 1976. Human malaria parasites in continuous culture. Science 193: 673–675.

    PubMed  Article  CAS  Google Scholar 

  25. Tyler, V.E. 1993. The honest herbal, 325–326. New York: Pharmaceutical Product Press.

    Google Scholar 

  26. Ward, S.A., N. Fisher, A. Hill, A. Mbekeani, A. Shone, G. Nixon, P. Stocks, P. Gibbons, R. Amewu, D.W. Hong, V. Barton, C. Pidathala, J. Chadwick, L. Le Pensee, A. Warman, R. Sharma, N.G. Berry, P.M. O’Neill, and G.A. Biagini. 2010. A novel drug for uncomplicated malaria: targeted high throughput screening (HTS) against the type II NADH:ubiquinone oxidoreductase (PfNdh2) of Plasmodium falciparum. Malaria Journal 9: I14.

    Article  Google Scholar 

  27. Wright, C.W., and J.D. Philipson. 1990. Natural products and the development of selective antiprotozoal. Phytotherapy Research 4: 127–139.

    Article  CAS  Google Scholar 

  28. Yildirim, A., A. Mavi, and A.A. Kara. 2001. Determination of antioxidant and antimicrobial activities of Rumex crispus L. extracts. Journal of Agriculture and Food Chemistry 49: 4083–4089.

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Ki-Hyeong Rhee.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lee, K.H., Rhee, KH. Antimalarial activity of nepodin isolated from Rumex crispus . Arch. Pharm. Res. 36, 430–435 (2013). https://doi.org/10.1007/s12272-013-0055-0

Download citation

Keywords

  • Malaria
  • Rumex crispus
  • NADH:quinone oxidoreductase enzyme
  • Plasmodium falciparum
  • Nepodin